Conditions have been developed for directly detecting protein-protein complexes by electrospray ionization mass spectrometry. To date, we have successfully detected strongly associated complexes, such as the p42/p62 heterodimer. p42/p62 is a TBP associated factor (TAF) that shares sequence homology with histones H3/H4. We are currently trying to determine the relationship between our ability to measure non-covalent complexes in the gas phase and the strength of the associations between the same partners in solution. Partial results of this study were reported in Nature 38 (1996) 316322.